Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
TOWARD THE RATIONAL DESIGN OF ANTIRETROVIRAL THERAPY FOR HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION
The Human Retroviruses. Gallo RC and Jay G, eds. San Diego, Academic Press, p. 335-78, 1991.. Unique Identifier : AIDSLINE ICDB/92678734 Mitsuya H; Broder S; Clinical Oncology Program, NCI, Bethesda, MD 20892
Abstract:
Replication of HIV can be suppressed in patients with HIV-related diseases by several antiretroviral agents. One such drug, 3'-azido-2',3'-dideoxynucleoside (AZT or zidovudine), has been formally shown to confer prolonged survival and improved quality of life in patients with advanced HIV infection. In theory, antiviral drugs exert their effects by interacting with viral structural components, virally encoded enzymes, viral genomes or proteins, cellular receptors, cellular enzymes, or factors needed for viral replication. Advances in retroviral therapy against AIDS are reviewed under the following headings: genetic organization of HIV; possible targets for therapeutic intervention (inhibition of viral binding to target cells, inhibition of later stages of viral entry, reverse transcriptase and viral protease as targeted molecules, migration of proviral DNA and its integration, transcription and translation [tat gene, rev gene, nef gene, and antiviral agents targeting the transcription/translation stage], maturation, transport, and assembly of viral components [glycosidase inhibitors, myristoylation inhibitors and others], and the viral budding process); DNA-chain terminators as antiretroviral agents (activity of 2',3'=dideoxynucleosides against HIV and structure/activity relationships in 2',3'-dideoxynucleoside analogs); 2',3'-dideoxynucleosides as therapeutics in human infection (AZT [clinical activity and emergence of AZT-insensitive HIV variants], ddC, and ddl); carbocyclic and acyclic nucleoside analogs active against HIV in vitro; and combination of antiretroviral drugs for therapy against AIDS. Major advances in the development of anti-HIV drugs will require adherence to the principles of randomized, controlled trials, using careful monitoring and effective trial termination rules by independent review boards. Such trials should provide an effective safeguard against investigator bias and protect patients and society against the possibility of commercial exploitation. (246 Refs)
Keywords: Acquired Immunodeficiency Syndrome/DRUG THERAPY/GENETICS/ MICROBIOLOGY Antiviral Agents/ADVERSE EFFECTS/*THERAPEUTIC USE Drug Therapy, Combination DNA Replication/*DRUG EFFECTS/GENETICS Gene Expression Regulation, Viral/*DRUG EFFECTS/PHYSIOLOGY Human HIV/*DRUG EFFECTS/GENETICS HIV Infections/*DRUG THERAPY/GENETICS/MICROBIOLOGY Structure-Activity Relationship MONOGRAPH REVIEW
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
